Methionine synthase alamin form

Figure 21-3. The methionine synthase reaction. Methionine synthase catalyzes the remethylation of homocysteine to methionine. In the first half reaction (1), a methyl group is transferred from 5-methyl tetrahydrofolate (5-MTHF) to the reduced form of cobalamin [Cob(I)], generating methyl-cobalamin [Methyl-Cob(III)] and tetrahydrofolate (THF). During the second half reaction (2), the methyl group is transferred from methylcobalamin to homocysteine, generating methionine. During the catalytic reaction, Cob(I) occasionally becomes oxidized, producing an inactive form of cobalamin, cob(II)alamin [Cob(II)]. The enzyme methionine synthase reductase (MTRR) then reactivates Cob(II) through reductive methylation, producing methyl-Cob(III). SAM, 5-adenosylmethionine SAH, 5-adeno-sylhomocysteine.

Cobalamin-dependent methionine synthase contains a built-in repair mechanism. If accidental oxidation of cob(I)alamin leads to inactive cob(lI)alamin, then the enzyme employs SAM and reduced flavodoxin to regenerate cob(I)alamin. Although the redox equilibrium below lies mainly on the left side, any cob(l)alamin formed is trapped by SAM-dependent methylation to yield methylcobalamin. 

Figure 2, Catalysis and reactivation of methionine synthase. Methionine for,motion occurs via two half reactions in which cobalamin serves as the intermediate methyl carrier. Reactivation is depicted in the right-hand portion of the diagram. An electron donor and AdoMet convert the inactive cob(II)alamin form of the enzyme to methylcob(III)alamin. In E. colU flavodoxin serves as the reductant for this priming reaction (7).

Fig. 12. Schematic illustration of the methyl group transfer steps catalyzed by methionine synthase from E. coli (Enz signifies apoenz3une). In the catal3d ic cycle, the corrinoid shuttles between methyl-cobalamin (3), in a base-of6fiIis-on form, and cob(I)alamin (6") (10).

Vitamin B12 must be converted into its coenzyme forms, adenosylcobalamin and methylcobalamin, in the cell. These coenzymes function as cofactors of methylmalonyl-CoA mutase and methionine synthase, respectively. Chronic kidney disease (CKD) may affect the conversion from vitamin B12 to the coenzyme forms. This section describes the intracellular metabolism of cyanocobalamin, which is included in many dietary supplements, in particular, referring to a recently discovered trafficking chaperone called methylmalonic aciduria cdlC type with homocystinuria (MMACHC). Cyanocobalamin is first converted to cob(II)alamin, which has no cyanogen group on the ligand occupying the upper axial position of the cobalamin structure. Cob(II)alamin is further reduced to cob(I)alamin, which can function as a coenzyme in the body. 

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